Tweet
_|SELECTED RESEARCH ARTICLES ABSTRACTS: 12 MAY 2008|_
[In this post: (1) Research Articles Abstracts.
Contents:
(1.1) Genetic characterization of H1N1, H1N2 and H3N2 swine influenza virus in Thailand.
(1.2) Agonists of Proteinase-Activated Receptor-2 Enhance IFN-{gamma}-Inducible Effects on Human Monocytes: Role in Influenza A Infection.
(1.3) A Broadly Protective Vaccine against Globally Dispersed Clade 1 and Clade 2 H5N1 Influenza Viruses.
(1.4) The role of initiating NTP concentrations in the regulation of influenza virus replication and transcription.
(1.5) Cost-effectiveness of live attenuated influenza vaccine versus inactivated influenza vaccine among children aged 24-59 months in the United States.
(1.6) DNA fusion vaccines incorporating IL-23 or RANTES for use in immunization against influenza.
(1.7) Polylactide-co-glycolide (PLG) microparticles modify the immune response to DNA vaccination.
(1.8) Genetically destined potentials for N-linked glycosylation of influenza virus hemagglutinin.
(1.9) Limited compatibility between the RNA polymerase components of influenza virus type A and B.
See original abstracts at the source site. EDITED.]
---------
-
(1.1): Arch Virol. 2008 May 6 [Epub ahead of print]
Genetic characterization of H1N1, H1N2 and H3N2 swine influenza virus in Thailand.
Chutinimitkul S, Thippamom N, Damrongwatanapokin S, Payungporn S, Thanawongnuwech R, Amonsin A, Boonsuk P, Sreta D, Bunpong N, Tantilertcharoen R, Chamnanpood P, Parchariyanon S, Theamboonlers A, Poovorawan Y. Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Swine have been known to be a suitable host for influenza A virus.
In Thailand, phylogenetic analysis on swine influenza virus (SIV) has as yet not been attempted.
The present report presents molecular and phylogenetic analysis performed on SIV in Thailand.
In this study, 12 SIV isolates from the central and eastern part of Thailand were subtyped and the molecular genetics of hemagglutinin and neuraminidase were elucidated.
Three subtypes, H1N1, H1N2 and H3N2, are described.
Phylogenetic analysis of the SIV hemagglutinin and neuraminidase genes shows individual clusters with swine, human or avian influenza virus at various global locations.
Furthermore, amino acid substitutions were detected either at the receptor binding site or the antigenic sites of the hemagglutinin gene.
PMID: 18458812 [PubMed - as supplied by publisher]
-
-------
-
(1.2): J Immunol. 2008 May 15;180(10):6903-10.
Agonists of Proteinase-Activated Receptor-2 Enhance IFN-{gamma}-Inducible Effects on Human Monocytes: Role in Influenza A Infection.
Feld M, Shpacovitch VM, Ehrhardt C, Kerkhoff C, Hollenberg MD, Vergnolle N, Ludwig S, Steinhoff M. Department of Dermatology, Interdisziplin?res Zentrum f?r Klinische Forschung M?nster, and Boltzmann Institute for Immunobiology of the Skin.
Proteinase-activated receptor-2 (PAR(2)) is expressed by different types of human leukocytes and involved in the development of inflammatory and infectious diseases.
However, its precise role in the regulation of human monocyte and macrophage function during viral infection remains unclear.
Also, the ability of PAR(2) agonists to enhance the effects induced by immune mediators during infection or inflammation is still poorly investigated.
Therefore, we investigated the ability of a PAR(2) agonist to enhance IFN-gamma-induced suppression of influenza A virus replication in human monocytes.
We found that this effect correlates with an increased abundance of IkappaBalpha after costimulation of cells with PAR(2) agonist and IFN-gamma.
Remarkably, coapplication of PAR(2) agonist and IFN-gamma also enhances the effects of IFN-gamma on IFN-gamma-inducible protein 10 kDa release, and CD64 and alphaVbeta3 surface expression by human monocytes.
Together, these findings indicate a potentially protective role of PAR(2) activation during the progression of influenza A virus infection.
This effect could be associated with the ability of PAR(2) agonists to enhance IFN-gamma-induced protective effects on human monocytes.
PMID: 18453611 [PubMed - in process]
-
-------
-
(1.3): J Infect Dis. 2008 Apr 15;197(8):1185-1188.
A Broadly Protective Vaccine against Globally Dispersed Clade 1 and Clade 2 H5N1 Influenza Viruses.
Hoelscher MA, Singh N, Garg S, Jayashankar L, Veguilla V, Pandey A, Matsuoka Y, Katz JM, Donis R, Mittal SK, Sambhara S. 1Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and 2Department of Comparative Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana.
Development of effective and immunogenic vaccines against highly pathogenic avian influenza H5N1 viruses with the potential to cause a pandemic is a public health priority.
The global demand for a vaccine cannot be met in the event of an influenza pandemic because of the limited capacity to manufacture egg-derived vaccines as well as potential problems with the availability of embryonated eggs.
Thus, there is an urgent need to develop alternative, egg-independent vaccines.
We developed an adenoviral vector-based vaccine that contains hemagglutinin protein from clade 1 and clade 2 viruses, as well as conserved nucleoprotein, to broaden the vaccine coverage against H5N1 viruses.
PMID: 18462165 [PubMed - as supplied by publisher]
-
-------
-
(1.4): J Virol. 2008 May 7 [Epub ahead of print]
The role of initiating NTP concentrations in the regulation of influenza virus replication and transcription.
Vreede FT, Gifford H, Brownlee GG. Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
The mechanisms regulating the synthesis of mRNA, cRNA and vRNA by the influenza A virus RNA-dependent RNA polymerase are not fully understood.
Previous studies in our laboratory have shown that virion-derived viral ribonucleoprotein complexes synthesize both mRNA and cRNA, in vitro and early in the infection cycle in vivo.
Our further studies showed that de novo synthesis of cRNA in vitro is more sensitive than capped primer-dependent synthesis of mRNA to the concentration of ATP, CTP and GTP.
Using rescued recombinant influenza A/WSN/33 viruses, we now demonstrate that the 3' terminal sequence of the vRNA promoter dictates the requirement for a high NTP concentration during de novo initiated replication to cRNA, whereas this is not the case for extension of capped primers during transcription to mRNA.
In contrast to some other viral polymerases for which only the initiating NTP is required at high concentrations, influenza virus polymerase requires high concentrations of the first three NTPs.
In addition, we show that base-pair mutations in the vRNA promoter can lead to non-templated dead-end mutations during replication to cRNA in vivo.
Based on our observations, we propose a new model for the de novo initiation of influenza virus replication.
PMID: 18463155 [PubMed - as supplied by publisher]
-
-------
-
(1.5): Vaccine. 2008 Apr 29 [Epub ahead of print]
Cost-effectiveness of live attenuated influenza vaccine versus inactivated influenza vaccine among children aged 24-59 months in the United States.
Luce BR, Nichol KL, Belshe RB, Frick KD, Li SX, Boscoe A, Rousculp MD, Mahadevia PJ. United BioSource Corporation, Bethesda, MD, USA.
BACKGROUND:
The US Advisory Committee on Immunization Practices (ACIP) recently expanded the influenza vaccine recommendation to include children 24-59 months of age. In a large head-to-head randomized controlled trial, live attenuated influenza vaccine, trivalent (LAIV) demonstrated a 54% relative reduction in culture-confirmed influenza illness compared with trivalent inactivated influenza vaccine (TIV) among children aged 24-59 months.
OBJECTIVE:
To evaluate the relative cost and benefit between two influenza vaccines (LAIV and TIV) for healthy children 24-59 months of age.
METHODS:
Using patient-level data from the clinical trial supplemented with cost data from published literature, we modeled the cost-effectiveness of these two vaccines. Effectiveness was measured in quality-adjusted life years (QALY) and cases of influenza avoided. The analysis used the societal perspective.
RESULTS:
Due to its higher acquisition cost, LAIV increased vaccination costs by $7.72 per child compared with TIV. However, compared with TIV, LAIV reduced the number of influenza illness cases and lowered the subsequent healthcare use of children and productivity losses of parents. The estimated offsets in direct and indirect costs saved $15.80 and $37.72 per vaccinated child, respectively. LAIV had a net total cost savings of $45.80 per child relative to TIV. One-way and probabilistic sensitivity analyses indicated that the model was robust across a wide range of relative vaccine efficacy and cost estimates.
CONCLUSIONS:
Due to its increased relative vaccine efficacy over TIV, LAIV reduced the burden of influenza and lowered both direct health care and societal costs among children 24-59 months of age.
PMID: 18462851 [PubMed - as supplied by publisher]
-
--------
-
(1.6): Vaccine. 2008 Apr 18 [Epub ahead of print]
DNA fusion vaccines incorporating IL-23 or RANTES for use in immunization against influenza.
Williman J, Young S, Buchan G, Slobbe L, Wilson M, Pang P, Austyn J, Preston S, Baird M. Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
The incorporation of RANTES or IL-23 into DNA vaccines may improve their immunogenicity by the recruitment and activation of dendritic cells.
This may also select for a TH1 response counteracting the TH2 response which can predominate when a DNA vaccine is delivered by gene gun.
We have immunized mice with various DNA constructs encoding APR/8/34 influenza virus hemagglutinin (HA), either fused to or separate from, IL-23 or RANTES using a gene gun.
Those immunized with IL-23/HA fusion constructs and challenged with influenza 27 weeks post-vaccination, tended to have cleared more virus than those vaccinated with HA DNA.
Mice immunized with the RANTES/HA fusion construct produced a mixed TH1/TH2 response whereas in HA-vaccinated mice, a TH2 response predominated.
Immunization with a plasmid in which HA and RANTES were under the control of separate promoters, failed to generate a mixed TH1/TH2 response suggesting that enhanced antigen uptake via RANTES receptors may contribute to the mixed immune response generated to the fusion construct.
Overall these findings provide further evidence that Type 1 cytokines or chemokines, fused to antigen in a DNA vaccine, can influence the nature and the longevity of the immune response and ultimately, its protective capacity.
PMID: 18456374 [PubMed - as supplied by publisher]
-
----------
-
(1.7): Vaccine. 2008 Feb 6;26(6):753-61. Epub 2007 Dec 26.
Polylactide-co-glycolide (PLG) microparticles modify the immune response to DNA vaccination.
Helson R, Olszewska W, Singh M, Megede JZ, Melero JA, O'Hagan D, Openshaw PJ. Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College, St. Mary's Campus, Paddington, London W2 1PG, UK.
Priming with the major surface glycoprotein G of respiratory syncytial virus (RSV) expressed by recombinant vaccinia leads to strong Th2 responses and lung eosinophilia during viral challenge.
We now show that DNA vaccination in BALB/c mice with plasmids encoding G attenuated RSV replication but also enhanced disease with lung eosinophilia and increased IL-4/5 production.
However, formulating the DNA with PLG microparticles reduced the severity of disease during RSV challenge without significantly lessening protection against viral replication.
PLG formulation greatly reduced lung eosinophilia and prevented the induction of IL-4 and IL-5 during challenge, accompanied by a less marked CD4+ T cell response and a restoration of the CD8+ T cell recruitment seen during infection of non-vaccinated animals.
After RSV challenge, lung eosinophilia was enhanced and prolonged in mice vaccinated with DNA encoding a secreted form of G; this effect was virtually prevented by PLG formulation.
Therefore, PLG microparticulate formulation modifies the pattern of immune responses induced by DNA vaccination boosts CD8+ T cell priming and attenuates Th2 responses.
We speculate that PLG microparticles affect antigen uptake and processing, thereby influencing the outcome of DNA vaccination.
PMID: 18191308 [PubMed - indexed for MEDLINE]
-
-------
-
(1.8): Virology. 2008 May 2 [Epub ahead of print]
Genetically destined potentials for N-linked glycosylation of influenza virus hemagglutinin.
Igarashi M, Ito K, Kida H, Takada A. Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan.
The addition of oligosaccharide side chains to influenza virus hemagglutinin (HA) is believed to facilitate viral escape from immune pressure in the human population.
To determine the implicit potentials for acquisition of N-linked glycosylation, we analyzed the genetic background of 16 subtypes of avian influenza virus, some of which may be potential pandemic viruses in the future.
We found a significant difference among HA subtypes in their genomic sequences to produce N-glycosylation sites.
Notably, recently circulating avian influenza viruses of the H5 and H9 subtypes may have rather greater capacities to undergo mutations associated with glycosylation of HA than past pandemic viruses.
We hypothesize that influenza viruses maintained in natural reservoirs could have different potentials for sustained circulation, depending on their HA subtypes, if introduced into the human population.
PMID: 18456302 [PubMed - as supplied by publisher]
-
-------
-
(1.9): Virus Res. 2008 May 1 [Epub ahead of print]
Limited compatibility between the RNA polymerase components of influenza virus type A and B.
Iwatsuki-Horimoto K, Hatta Y, Hatta M, Muramoto Y, Chen H, Kawaoka Y, Horimoto T. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Reassortants between type A and B influenza viruses have not been detected in nature, although both viruses co-circulate in human populations.
One explanation for this may be functional incompatibility of RNA transcription and replication between type A and B viruses.
To test this possibility, we constructed type A/B mosaic polymerase machinery, containing PB2, PB1, PA and nucleoprotein from each of the two virus types, and assessed their polymerase activities with a type A promoter in a reporter assay.
Type B polymerase machinery containing homologous components was functional with the type A promoter albeit to various extents depending on the segments from which the regions downstream of the promoter sequence were derived, indicating functional compatibility between the type A promoter and B polymerase machinery.
However, all of the A/B mosaic polymerase machinery, except that containing PA from a type A and the others from a type B virus strain, did not function with the type A promoter, indicating limited compatibility among polymerase components of both types.
Taken together, these data suggest that incompatibility among components of the polymerase machinery for RNA transcription and replication alone is not responsible for the lack of heterotypic reassortants.
PMID: 18455827 [PubMed - as supplied by publisher]
-
------
Contents:
(1.1) Genetic characterization of H1N1, H1N2 and H3N2 swine influenza virus in Thailand.
(1.2) Agonists of Proteinase-Activated Receptor-2 Enhance IFN-{gamma}-Inducible Effects on Human Monocytes: Role in Influenza A Infection.
(1.3) A Broadly Protective Vaccine against Globally Dispersed Clade 1 and Clade 2 H5N1 Influenza Viruses.
(1.4) The role of initiating NTP concentrations in the regulation of influenza virus replication and transcription.
(1.5) Cost-effectiveness of live attenuated influenza vaccine versus inactivated influenza vaccine among children aged 24-59 months in the United States.
(1.6) DNA fusion vaccines incorporating IL-23 or RANTES for use in immunization against influenza.
(1.7) Polylactide-co-glycolide (PLG) microparticles modify the immune response to DNA vaccination.
(1.8) Genetically destined potentials for N-linked glycosylation of influenza virus hemagglutinin.
(1.9) Limited compatibility between the RNA polymerase components of influenza virus type A and B.
See original abstracts at the source site. EDITED.]
---------
-
(1.1): Arch Virol. 2008 May 6 [Epub ahead of print]
Genetic characterization of H1N1, H1N2 and H3N2 swine influenza virus in Thailand.
Chutinimitkul S, Thippamom N, Damrongwatanapokin S, Payungporn S, Thanawongnuwech R, Amonsin A, Boonsuk P, Sreta D, Bunpong N, Tantilertcharoen R, Chamnanpood P, Parchariyanon S, Theamboonlers A, Poovorawan Y. Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Swine have been known to be a suitable host for influenza A virus.
In Thailand, phylogenetic analysis on swine influenza virus (SIV) has as yet not been attempted.
The present report presents molecular and phylogenetic analysis performed on SIV in Thailand.
In this study, 12 SIV isolates from the central and eastern part of Thailand were subtyped and the molecular genetics of hemagglutinin and neuraminidase were elucidated.
Three subtypes, H1N1, H1N2 and H3N2, are described.
Phylogenetic analysis of the SIV hemagglutinin and neuraminidase genes shows individual clusters with swine, human or avian influenza virus at various global locations.
Furthermore, amino acid substitutions were detected either at the receptor binding site or the antigenic sites of the hemagglutinin gene.
PMID: 18458812 [PubMed - as supplied by publisher]
-
-------
-
(1.2): J Immunol. 2008 May 15;180(10):6903-10.
Agonists of Proteinase-Activated Receptor-2 Enhance IFN-{gamma}-Inducible Effects on Human Monocytes: Role in Influenza A Infection.
Feld M, Shpacovitch VM, Ehrhardt C, Kerkhoff C, Hollenberg MD, Vergnolle N, Ludwig S, Steinhoff M. Department of Dermatology, Interdisziplin?res Zentrum f?r Klinische Forschung M?nster, and Boltzmann Institute for Immunobiology of the Skin.
Proteinase-activated receptor-2 (PAR(2)) is expressed by different types of human leukocytes and involved in the development of inflammatory and infectious diseases.
However, its precise role in the regulation of human monocyte and macrophage function during viral infection remains unclear.
Also, the ability of PAR(2) agonists to enhance the effects induced by immune mediators during infection or inflammation is still poorly investigated.
Therefore, we investigated the ability of a PAR(2) agonist to enhance IFN-gamma-induced suppression of influenza A virus replication in human monocytes.
We found that this effect correlates with an increased abundance of IkappaBalpha after costimulation of cells with PAR(2) agonist and IFN-gamma.
Remarkably, coapplication of PAR(2) agonist and IFN-gamma also enhances the effects of IFN-gamma on IFN-gamma-inducible protein 10 kDa release, and CD64 and alphaVbeta3 surface expression by human monocytes.
Together, these findings indicate a potentially protective role of PAR(2) activation during the progression of influenza A virus infection.
This effect could be associated with the ability of PAR(2) agonists to enhance IFN-gamma-induced protective effects on human monocytes.
PMID: 18453611 [PubMed - in process]
-
-------
-
(1.3): J Infect Dis. 2008 Apr 15;197(8):1185-1188.
A Broadly Protective Vaccine against Globally Dispersed Clade 1 and Clade 2 H5N1 Influenza Viruses.
Hoelscher MA, Singh N, Garg S, Jayashankar L, Veguilla V, Pandey A, Matsuoka Y, Katz JM, Donis R, Mittal SK, Sambhara S. 1Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and 2Department of Comparative Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana.
Development of effective and immunogenic vaccines against highly pathogenic avian influenza H5N1 viruses with the potential to cause a pandemic is a public health priority.
The global demand for a vaccine cannot be met in the event of an influenza pandemic because of the limited capacity to manufacture egg-derived vaccines as well as potential problems with the availability of embryonated eggs.
Thus, there is an urgent need to develop alternative, egg-independent vaccines.
We developed an adenoviral vector-based vaccine that contains hemagglutinin protein from clade 1 and clade 2 viruses, as well as conserved nucleoprotein, to broaden the vaccine coverage against H5N1 viruses.
PMID: 18462165 [PubMed - as supplied by publisher]
-
-------
-
(1.4): J Virol. 2008 May 7 [Epub ahead of print]
The role of initiating NTP concentrations in the regulation of influenza virus replication and transcription.
Vreede FT, Gifford H, Brownlee GG. Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
The mechanisms regulating the synthesis of mRNA, cRNA and vRNA by the influenza A virus RNA-dependent RNA polymerase are not fully understood.
Previous studies in our laboratory have shown that virion-derived viral ribonucleoprotein complexes synthesize both mRNA and cRNA, in vitro and early in the infection cycle in vivo.
Our further studies showed that de novo synthesis of cRNA in vitro is more sensitive than capped primer-dependent synthesis of mRNA to the concentration of ATP, CTP and GTP.
Using rescued recombinant influenza A/WSN/33 viruses, we now demonstrate that the 3' terminal sequence of the vRNA promoter dictates the requirement for a high NTP concentration during de novo initiated replication to cRNA, whereas this is not the case for extension of capped primers during transcription to mRNA.
In contrast to some other viral polymerases for which only the initiating NTP is required at high concentrations, influenza virus polymerase requires high concentrations of the first three NTPs.
In addition, we show that base-pair mutations in the vRNA promoter can lead to non-templated dead-end mutations during replication to cRNA in vivo.
Based on our observations, we propose a new model for the de novo initiation of influenza virus replication.
PMID: 18463155 [PubMed - as supplied by publisher]
-
-------
-
(1.5): Vaccine. 2008 Apr 29 [Epub ahead of print]
Cost-effectiveness of live attenuated influenza vaccine versus inactivated influenza vaccine among children aged 24-59 months in the United States.
Luce BR, Nichol KL, Belshe RB, Frick KD, Li SX, Boscoe A, Rousculp MD, Mahadevia PJ. United BioSource Corporation, Bethesda, MD, USA.
BACKGROUND:
The US Advisory Committee on Immunization Practices (ACIP) recently expanded the influenza vaccine recommendation to include children 24-59 months of age. In a large head-to-head randomized controlled trial, live attenuated influenza vaccine, trivalent (LAIV) demonstrated a 54% relative reduction in culture-confirmed influenza illness compared with trivalent inactivated influenza vaccine (TIV) among children aged 24-59 months.
OBJECTIVE:
To evaluate the relative cost and benefit between two influenza vaccines (LAIV and TIV) for healthy children 24-59 months of age.
METHODS:
Using patient-level data from the clinical trial supplemented with cost data from published literature, we modeled the cost-effectiveness of these two vaccines. Effectiveness was measured in quality-adjusted life years (QALY) and cases of influenza avoided. The analysis used the societal perspective.
RESULTS:
Due to its higher acquisition cost, LAIV increased vaccination costs by $7.72 per child compared with TIV. However, compared with TIV, LAIV reduced the number of influenza illness cases and lowered the subsequent healthcare use of children and productivity losses of parents. The estimated offsets in direct and indirect costs saved $15.80 and $37.72 per vaccinated child, respectively. LAIV had a net total cost savings of $45.80 per child relative to TIV. One-way and probabilistic sensitivity analyses indicated that the model was robust across a wide range of relative vaccine efficacy and cost estimates.
CONCLUSIONS:
Due to its increased relative vaccine efficacy over TIV, LAIV reduced the burden of influenza and lowered both direct health care and societal costs among children 24-59 months of age.
PMID: 18462851 [PubMed - as supplied by publisher]
-
--------
-
(1.6): Vaccine. 2008 Apr 18 [Epub ahead of print]
DNA fusion vaccines incorporating IL-23 or RANTES for use in immunization against influenza.
Williman J, Young S, Buchan G, Slobbe L, Wilson M, Pang P, Austyn J, Preston S, Baird M. Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
The incorporation of RANTES or IL-23 into DNA vaccines may improve their immunogenicity by the recruitment and activation of dendritic cells.
This may also select for a TH1 response counteracting the TH2 response which can predominate when a DNA vaccine is delivered by gene gun.
We have immunized mice with various DNA constructs encoding APR/8/34 influenza virus hemagglutinin (HA), either fused to or separate from, IL-23 or RANTES using a gene gun.
Those immunized with IL-23/HA fusion constructs and challenged with influenza 27 weeks post-vaccination, tended to have cleared more virus than those vaccinated with HA DNA.
Mice immunized with the RANTES/HA fusion construct produced a mixed TH1/TH2 response whereas in HA-vaccinated mice, a TH2 response predominated.
Immunization with a plasmid in which HA and RANTES were under the control of separate promoters, failed to generate a mixed TH1/TH2 response suggesting that enhanced antigen uptake via RANTES receptors may contribute to the mixed immune response generated to the fusion construct.
Overall these findings provide further evidence that Type 1 cytokines or chemokines, fused to antigen in a DNA vaccine, can influence the nature and the longevity of the immune response and ultimately, its protective capacity.
PMID: 18456374 [PubMed - as supplied by publisher]
-
----------
-
(1.7): Vaccine. 2008 Feb 6;26(6):753-61. Epub 2007 Dec 26.
Polylactide-co-glycolide (PLG) microparticles modify the immune response to DNA vaccination.
Helson R, Olszewska W, Singh M, Megede JZ, Melero JA, O'Hagan D, Openshaw PJ. Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College, St. Mary's Campus, Paddington, London W2 1PG, UK.
Priming with the major surface glycoprotein G of respiratory syncytial virus (RSV) expressed by recombinant vaccinia leads to strong Th2 responses and lung eosinophilia during viral challenge.
We now show that DNA vaccination in BALB/c mice with plasmids encoding G attenuated RSV replication but also enhanced disease with lung eosinophilia and increased IL-4/5 production.
However, formulating the DNA with PLG microparticles reduced the severity of disease during RSV challenge without significantly lessening protection against viral replication.
PLG formulation greatly reduced lung eosinophilia and prevented the induction of IL-4 and IL-5 during challenge, accompanied by a less marked CD4+ T cell response and a restoration of the CD8+ T cell recruitment seen during infection of non-vaccinated animals.
After RSV challenge, lung eosinophilia was enhanced and prolonged in mice vaccinated with DNA encoding a secreted form of G; this effect was virtually prevented by PLG formulation.
Therefore, PLG microparticulate formulation modifies the pattern of immune responses induced by DNA vaccination boosts CD8+ T cell priming and attenuates Th2 responses.
We speculate that PLG microparticles affect antigen uptake and processing, thereby influencing the outcome of DNA vaccination.
PMID: 18191308 [PubMed - indexed for MEDLINE]
-
-------
-
(1.8): Virology. 2008 May 2 [Epub ahead of print]
Genetically destined potentials for N-linked glycosylation of influenza virus hemagglutinin.
Igarashi M, Ito K, Kida H, Takada A. Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan.
The addition of oligosaccharide side chains to influenza virus hemagglutinin (HA) is believed to facilitate viral escape from immune pressure in the human population.
To determine the implicit potentials for acquisition of N-linked glycosylation, we analyzed the genetic background of 16 subtypes of avian influenza virus, some of which may be potential pandemic viruses in the future.
We found a significant difference among HA subtypes in their genomic sequences to produce N-glycosylation sites.
Notably, recently circulating avian influenza viruses of the H5 and H9 subtypes may have rather greater capacities to undergo mutations associated with glycosylation of HA than past pandemic viruses.
We hypothesize that influenza viruses maintained in natural reservoirs could have different potentials for sustained circulation, depending on their HA subtypes, if introduced into the human population.
PMID: 18456302 [PubMed - as supplied by publisher]
-
-------
-
(1.9): Virus Res. 2008 May 1 [Epub ahead of print]
Limited compatibility between the RNA polymerase components of influenza virus type A and B.
Iwatsuki-Horimoto K, Hatta Y, Hatta M, Muramoto Y, Chen H, Kawaoka Y, Horimoto T. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Reassortants between type A and B influenza viruses have not been detected in nature, although both viruses co-circulate in human populations.
One explanation for this may be functional incompatibility of RNA transcription and replication between type A and B viruses.
To test this possibility, we constructed type A/B mosaic polymerase machinery, containing PB2, PB1, PA and nucleoprotein from each of the two virus types, and assessed their polymerase activities with a type A promoter in a reporter assay.
Type B polymerase machinery containing homologous components was functional with the type A promoter albeit to various extents depending on the segments from which the regions downstream of the promoter sequence were derived, indicating functional compatibility between the type A promoter and B polymerase machinery.
However, all of the A/B mosaic polymerase machinery, except that containing PA from a type A and the others from a type B virus strain, did not function with the type A promoter, indicating limited compatibility among polymerase components of both types.
Taken together, these data suggest that incompatibility among components of the polymerase machinery for RNA transcription and replication alone is not responsible for the lack of heterotypic reassortants.
PMID: 18455827 [PubMed - as supplied by publisher]
-
------
Comment